1. Field of the Invention
The present invention relates to a mass spectrometer.
2. Discussion of the Prior Art
The duty cycle of an orthogonal acceleration Time of Flight (xe2x80x9coaTOFxe2x80x9d) mass analyser is typically in the region of 20-30% for ions of the maximum mass to charge ratio and less for ions with lower mass to charge ratios.
FIG. 1 illustrates part of the geometry of a conventional orthogonal acceleration Time of Flight mass analyser. In an orthogonal acceleration Time of Flight mass analyser ions are orthogonally accelerated into a drift region (not shown) by a pusher electrode 1 having a length L1. The distance between the pusher electrode 1 and the ion detector 2 may be defined as being L2. The time taken for ions to pass through the drift region, be reflected by a reflectron (not shown) and reach the ion detector 2 is the same as the time it would have taken for the ions to have travelled the axial distance L1+L2 from the centre of the pusher electrode 1 to the centre of the ion detector 2 had the ions not been accelerated into the drift region. The length of the ion detector 2 is normally at least L1 so as to eliminate losses.
If the Time of Flight mass analyser is designed to orthogonally accelerate ions having a maximum mass to charge ratio Mmax then the cycle time xcex94T between consecutive energisations of the pusher electrode 1 (and hence pulses of ions into the drift region) is the time required for ions of mass to charge ratio equal to Mmax to travel the axial distance L1+L2 from the pusher electrode 1 to the ion detector 2.
The duty cycle Dcy for ions with a mass to charge ratio M is given by:       D    cy    =            L1              L1        +        L2              ·                  M                  M          max                    
For example, if L1 is 35 mm and the distance L2 is 90 mm then the duty cycle for ions of maximum mass to charge value is given by L1/(L1+L2) which equals 28.0%.
Increasing L1 and/or decreasing L2 will in theory increase the duty cycle. However, increasing L1 would require a larger and hence more expensive ion detector 2 and this would also place a greater demand on mechanical alignment including grid flatness. Such an option is not therefore practical.
On the other hand, reducing L2 would also be impractical. Reducing L2 per se would shorten the flight time in the drift region and result in a loss of resolution. Alternatively, L2 could be reduced and the flight time kept constant by reducing the energy of the ions prior to them reaching the pusher electrode 1. However, this would result in ions which were less confined and there would be a resulting loss in transmission.
A person skilled in the art will therefore appreciate that for mechanical and physical reasons constraints are placed on the values that L1 and L2 can take, and this results in a typical maximum duty cycle in the range 20-30%.
It is known to trap and store ions upstream of the pusher electrode 1 in an ion trap which is non-mass selective i.e. the ion trap does not discriminate on the basis of mass to charge ratio but either traps all ions or releases all ions (by contrast a mass selective ion trap can release just some ions having specific mass to charge ratios whilst retaining others). All the ions trapped within the ion trap are therefore released in a packet or pulse of ions. Ions with different mass to charge values travel with different velocities to the pusher electrode 1 so that only certain ions are present adjacent the pusher electrode 1 when the pusher electrode 1 is energised so as to orthogonally accelerate ions into the drift region. Some ions will still be upstream of the pusher electrode 1 when the pusher electrode 1 is energised and other others will have already passed the pusher electrode 1 when the pusher electrode 1 is energised. Accordingly, only some of the ions released from the upstream ion trap will actually be orthogonally accelerated into the drift region of the Time of Flight mass analyser.
By arranging for the pusher electrode 1 to orthogonally accelerate ions a predetermined time after ions have been released from the ion trap it is possible to increase the duty cycle for some ions having a certain mass to charge ratio to approximately 100%. However, the duty cycle for ions having other mass to charge ratios may be much less than 100% and for a wide range of mass to charge ratios the duty cycle will be 0%.
The dashed line in FIG. 2 illustrates the duty cycle for an orthogonal acceleration Time of Flight mass analyser operated in a conventional manner without an upstream ion trap. The maximum mass to charge ratio is assume to be 1000, L1 was set to 35 mm and the distance L2 was set to 90 mm. The maximum duty cycle is 28% for ions of mass to charge ratio 1000 and for lower mass to charge ratio ions the duty cycle is much less.
The solid line in FIG. 2 illustrates how the duty cycle for some ions may be enhanced to approximately 100% when a non-mass selective upstream ion trap is used. In this case it is assumed that the distance from the ion trap to the pusher electrode 1 is 165 mm and that the pusher electrode 1 is arranged to be energized at a time after ions are released from the upstream ion trap such that ions having a mass to charge ratio of 300 are orthogonally accelerated with a resultant duty cycle of 100%. However, as is readily apparent from FIG. 2, the duty cycle for ions having smaller or larger mass to charge ratios decreases rapidly so that for ions having a mass to charge ratioxe2x89xa6200 and for ions having a mass to charge ratioxe2x89xa7450 the duty cycle is 0%. The known method of increasing the duty cycle for just some ions may be of interest if only a certain part of the mass spectrum is of interest such as for precursor ion discovery by the method of daughter ion scanning. However, it is of marginal or no benefit if a full mass spectrum is required.
It is therefore desired to provide a mass spectrometer which overcomes at least some of the disadvantages of the known arrangements.
According to an aspect of the present invention there is provided a mass spectrometer comprising: a mass selective ion trap; an orthogonal acceleration Time of Flight mass analyser arranged downstream of the ion trap, the orthogonal acceleration Time of Flight mass analyser comprising an electrode for orthogonally accelerating ions; and a control means for controlling the mass selective ion trap and the orthogonal acceleration Time of Flight mass analyser, wherein in a mode of operation the control means controls the ion trap and the orthogonal acceleration Time of Flight mass analyser so that: (i) at a first time t1 ions having mass to charge ratios within a first range are arranged to be substantially passed from the ion trap to the orthogonal acceleration Time of Flight mass analyser whilst ions having mass to charge ratios outside of the first range are not substantially passed to the orthogonal acceleration Time of Flight mass analyser; (ii) at a later time t1+xcex94t1 the electrode is arranged to orthogonally accelerate ions having mass to charge ratios within the first range; (iii) at a second later time t2 ions having mass to charge ratios within a second range are arranged to be substantially passed from the ion trap to the orthogonal acceleration Time of Flight mass analyser whilst ions having mass to charge ratios outside of the second range are not substantially passed to the orthogonal acceleration Time of Flight mass analyser; and (iv) at a later time t2+xcex94t2 the electrode is arranged to orthogonally accelerate ions having mass to charge ratios within the second range, wherein xcex94t1xe2x89xa0xcex94t2. Accordingly, ions are released from the ion trap and are orthogonally accelerated after a first delay and then further ions are released from the ion trap and are orthogonally accelerated after a second different delay time.
At the first time t1 ions having mass to charge ratios outside of the first range are preferably substantially retained within the ion trap. Likewise, at the second time t2 ions having mass to charge ratios outside of the second range are preferably substantially retained within the ion trap.
The first range preferably has a minimum mass to charge ratio M1min and a maximum mass to charge ratio M1max and wherein the value M1maxxe2x88x92M1min falls within a range of 1-50, 50-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500 or  greater than 1500.
Similarly, the second range preferably has a minimum mass to charge ratio M2min and a maximum mass to charge ratio M2max and wherein the value M2maxxe2x88x92M2min falls within a range of 1-50, 50-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500 or  greater than 1500.
The control means preferably further controls the ion trap and the orthogonal acceleration Time of Flight mass analyser so that: (v) at a third later time t3 ions having mass to charge ratios within a third range are arranged to be substantially passed from the ion trap to the orthogonal acceleration Time of Flight mass analyser whilst ions having mass to charge ratios outside of the third range are not substantially passed to the orthogonal acceleration Time of Flight mass analyser; and (vi) at a later time t3+xcex94t3 the electrode is arranged to orthogonally accelerate ions having mass to charge ratios within the third range, wherein xcex94t1xe2x89xa0xcex94t2xe2x89xa0xcex94t3.
At the third time t3 ions having mass to charge ratios outside of the third range are preferably substantially retained within the ion trap.
The third range preferably has a minimum mass to charge ratio M3min and a maximum mass to charge ratio M3max and wherein the value M3maxxe2x88x92M3min falls within a range of 1-50, 50-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500 or  greater than 1500.
The control means preferably further controls the ion trap and the orthogonal acceleration Time of Flight mass analyser so that: (vii) at a fourth later time t4 ions having mass to charge ratios within a fourth range are arranged to be substantially passed from the ion trap to the orthogonal acceleration Tire of Flight mass analyser whilst ions having mass to charge ratios outside of the fourth range are not substantially passed to the orthogonal acceleration Time of Flight mass analyser; and (viii) at a later time t4+xcex94t4 the electrode is arranged to orthogonally accelerate ions having mass to charge ratios within the fourth range, wherein xcex94t1xe2x89xa0xcex94t2xe2x89xa0xcex94t3xe2x89xa0xcex94t4.
At the fourth time t4 ions having mass to charge ratios outside of the fourth range are preferably substantially retained within the ion trap.
The fourth range preferably has a minimum mass to charge ratio M4min and a maximum mass to charge ratio M4max and wherein the value M4maxxe2x88x92M4min falls within a range of 1-50, 50-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500 or  greater than 1500. According to various embodiments at least five, six, seven, eight, nine, ten or more bunches of ions may be consecutively released from the ion trap and orthogonally accelerated after a delay time which preferably varies in each case.
The mass selective ion trap may be either a 3D quadrupole field ion trap, a magnetic (xe2x80x9cPenningxe2x80x9d) ion trap or a linear quadrupole ion trap.
The ion trap may comprise in use a gas so that ions enter the ion trap with energies such that the ions are collisionally cooled without substantially fragmenting upon colliding with the gas. Alternatively, ions may be arranged to enter the ion trap with energies such that at least 10% of the ions are caused to fragment upon colliding with the gas i.e. the ion trap also acts as a collision cell.
Ions may be released from the mass selective ion trap by mass-selective instability and/or by resonance ejection. If mass-selective instability is used to eject ions from the ion trap then the ion trap is either in a low pass mode or in a high pass mode. As such, M1max and/or M2max and/or M3max and/or M4max may in a high pass mode be at infinity. Likewise, in a low pass mode M1min and/or M2min and/or M3min and/or M4min may be zero. If resonance ejection is used to eject ions from the ion trap then the ion trap may be operated in either a low pass mode, high pass mode or bandpass mode. Other modes of operation are also possible.
The orthogonal acceleration Time of Flight mass analyser preferably comprises a drift region and an ion detector, wherein the electrode is arranged to orthogonally accelerate ions into the drift region. The mass spectrometer may further comprise an ion source, a quadrupole mass filter and a gas collision cell for collision induced fragmentation of ions.
According to an embodiment the mass spectrometer may comprise a continuous ion source such as an Electrospray ion source, an Atmospheric Pressure Chemical Ionisation (xe2x80x9cAPCIxe2x80x9d) ion source, an Electron Impact (xe2x80x9cEIxe2x80x9d) ion source, an Atmospheric Pressure Photon Ionisation (xe2x80x9cAPPIxe2x80x9d) ion source, a Chemical Ionisation (xe2x80x9cCIxe2x80x9d) ion source, a Fast Atom Bombardment (xe2x80x9cFABxe2x80x9d) ion source, a Liquid Secondary Ions Mass Spectrometry (xe2x80x9cLSIMSxe2x80x9d) ion source, an Inductively Coupled Plasma (xe2x80x9cICPxe2x80x9d) ion source, a Field Ionisation (xe2x80x9cFIxe2x80x9d) ion source, and a Field Desorption (xe2x80x9cFDxe2x80x9d) ion source.
For operation with a continuous ion source a further ion trap may be provided which continuously acquires ions from the ion source and traps them before releasing bunches of ions for storage in the mass selective ion trap. The further ion trap may comprise a linear RF multipole ion trap or a linear RF ring set (ion tunnel) ion trap. A linear RF ring set (ion tunnel) is preferred since it may have a series of programmable axial fields. The ion tunnel ion guide can act therefore not only as an ion guide but the ion tunnel ion guide can move ions along its length and retain or store ions at certain positions along its length. Hence, in the presence of a bath gas for collisional damping the ion tunnel ion guide can continuously receive ions from a ion source and store them at an appropriate position near the exit. If required it can also be used for collision induced fragmentation of those ions. It can then be programmed to periodically release ions for collection and storage in the ion trap.
Between each release of ions the mass selective ion trap may receive a packet of ions from the further ion trap. The trapping of ions in the ion trap may also be aided by the presence of a background gas or bath gas for collisional cooling of the ions. This helps quench their motion and improves trapping. In this way the mass selective ion trap may be periodically replenished with ions ready for release to the orthogonal acceleration Time of Flight mass analyser.
An arrangement incorporating two traps enables a high duty cycle to be obtained for all ions irrespective of their mass to charge value. A tandem quadrupole Time of Flight mass spectrometer may be provided comprising an ion source, an ion guide, a quadrupole mass filter, a gas collision cell for collision induced fragmentation, an 3D quadrupole ion trap, a further ion guide, and an orthogonal acceleration Time of Flight mass analyser. It will be apparent that the duty cycle will be increased compared with conventional arrangements irrespective of whether the mass spectrometer is operated in the MS (non-fragmentation) mode or MS/MS (fragmentation) mode.
According to another embodiment the mass spectrometer may comprise a pseudo-continuous ion source such as a Matrix Assisted Laser Desorption Ionisation (xe2x80x9cMALDIxe2x80x9d) ion source and a drift tube or drift region arranged so that ions become dispersed. The drift tube or drift region may also be provided with gas to collisionally cool ions.
According to another embodiment the mass spectrometer may comprise a pulsed ion source such as a Matrix Assisted Laser Desorption Ionisation (xe2x80x9cMALDIxe2x80x9d) ion source or a Laser Desorption Ionisation ion source.
Although a further ion trap is preferably provided upstream of the mass selective ion trap when a continuous ion source is provided, a further ion trap may be provided irrespective of the type of ion source being used. In a mode of operation the axial electric field along the further ion trap may be varied either temporally and/or spatially. In a mode of operation ions may be urged along the further ion trap by an axial electric field which varies along the length of the further ion trap. In a mode of operation at least a portion of the further ion trap may act as an AC or RF-only ion guide with a constant axial electric field. In a mode of operation at least a portion of the further ion trap may retain or store ions within one or more locations along the length of the further ion trap.
According to a particularly preferred embodiment the further ion trap may comprise an AC or RF ion tunnel ion trap comprising at least 4 electrodes having similar sized apertures through which ions are transmitted in use. The ion trap may comprise at least 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 such electrodes according to other embodiments.
According to less preferred embodiments the further ion trap may comprise a linear quadrupole ion trap, a linear hexapole, octopole or higher order multipole ion trap, a 3D quadrupole field ion trap or a magnetic (xe2x80x9cPenningxe2x80x9d) ion trap. The further ion trap may or may not therefore be mass selective itself.
The further ion trap preferably substantially continuously receives ions at one end.
The further ion trap may comprise in use a gas so that ions are arranged to either enter the further ion trap with energies such that the ions are collisionally cooled without substantially fragmenting upon colliding with the gas. Alternatively, ions may be arranged to enter the further ion trap with energies such that at least 10% of the ions are caused to fragment upon colliding with the gas i.e. the further ion trap acts as a collision cell.
The further ion trap preferably periodically releases ions and passes at least some of the ions to the mass selective ion trap.
According to another aspect of the present invention, there is provided a mass spectrometer comprising: a 3D quadrupole ion trap; an orthogonal acceleration Time of Flight mass analyser arranged downstream of the 3D quadrupole ion trap, the orthogonal acceleration Time of Flight mass analyser comprising an electrode for orthogonally accelerating ions; and control means for controlling the ion trap and the electrode, wherein the control means causes: (i) a first packet of ions having mass to charge ratios within a first range to be released from the ion trap and then the electrode to orthogonally accelerate the first packet of ions after a first delay time; and (ii) a second packet of ions having mass to charge ratios within a second (different) range to be released from the ion trap and then the electrode to orthogonally accelerate the second packet of ions after a second (different) delay time.
The control means preferably further causes: (iii) a third packet of ions having mass to charge ratios within a third (different) range to be released from the ion trap and then the electrode to orthogonally accelerate the third packet of ions after a third (different) delay time; and (iv) a fourth packet of ions having mass to charge ratios within a fourth (different) range to be released from the ion trap and then the electrode to orthogonally accelerate the fourth packet of ions after a fourth (different) delay time.
The first, second, third and fourth ranges are preferably all different and the first, second, third and fourth delay times are preferably all different. Preferably, at least the upper mass cut-off and/or the lower mass cut-off of the first, second, third and fourth ranges are different. The width of the first, second, third and fourth ranges may or may not be the same. According to other embodiments at least 5, 6, 7, 8, 9, 10 or more than 10 packets of ions may be released and orthogonally accelerated.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising: ejecting ions having mass to charge ratios within a first range from a mass selective ion trap whilst ions having mass to charge ratios outside of the first range are retained within the ion trap; orthogonally accelerating ions having mass to charge ratios within the first range after a first delay time; ejecting ions having mass to charge ratios within a second (different) range from a mass selective ion trap whilst ions having mass to charge ratios outside of the second range are retained within the ion trap; and orthogonally accelerating ions having mass to charge ratios within the second range after a second delay time different from the first delay time.
According to another aspect of the present invention there is provided a mass spectrometer comprising a mass selective ion trap upstream of an electrode for orthogonally accelerating ions, wherein in a mode of operation a first packet of ions is released from the ion trap and the electrode is energised after a first predetermined delay time, a second packet of ions is released from the ion trap and the electrode is energized after a second predetermined delay time, a third packet of ions is released from the ion trap and the electrode is energised after a third predetermined delay time, and a fourth packet of ions is released from the ion trap and the electrode is energised after a fourth predetermined delay time, wherein the first, second, third and fourth delay times are all different.
According to another aspect of the present invention, there is provided a mass spectrometer comprising a mass selective ion trap; and an orthogonal acceleration Time of Flight mass analyser having an electrode for orthogonally accelerating ions into a drift region; wherein multiple packets of ions are progressively released from the mass selective ion trap and are sequentially or serially ejected into the drift region after different delay times. The ions are progressively released according to their mass to charge ratios i.e. the ions are released in a mass to charge ratio selective manner.
According to another aspect of the present invention, there is provided a method of mass spectrometry comprising: progressively releasing multiple packets of ions from a mass selective ion trap so that the packets of ions are sequentially or serially ejected into a drift region of an orthogonal acceleration Time of Flight mass analyser by an electrode after different delay times. The ions are progressively released according to their mass to charge ratios i.e. the ions are released in a mass to charge ratio selective manner.
According to another aspect of the present invention there is provided a mass spectrometer comprising: a mass selective ion trap; an orthogonal acceleration Time of Flight mass analyser arranged downstream of the ion trap, the orthogonal acceleration Time of Flight mass analyser comprising an electrode for orthogonally accelerating ions; and a control means for controlling the mass selective ion trap and the orthogonal acceleration Time of Flight mass analyser, wherein in a mode of operation the control means controls the ion trap and the orthogonal acceleration Time of Flight mass analyser so that: (i) at a first time t1 ions having mass to charge ratios within a first range are arranged to be substantially passed from the ion trap to the orthogonal acceleration Time of Flight mass analyser whilst ions having mass to charge ratios outside of the first range are not substantially passed to the orthogonal acceleration Time of Flight mass analyser; (ii) at a second later time t2 after t1 ions having mass to charge ratios within a second range are arranged to be substantially passed from the ion trap to the orthogonal acceleration Time of Flight mass analyser whilst ions having mass to charge ratios outside of the second range are not substantially passed to the orthogonal acceleration Time of Flight mass analyser; and (iii) at a later time tpush after t1 and t2 the electrode is arranged to orthogonally accelerate ions having mass to charge ratios within the first and second ranges. The electrode is not energised in the time after t1 and prior to tpush.
According to a preferred embodiment ions are released from the mass selective ion trap in a pulsed manner as a number of discrete packets of ions. However, according to another embodiment the mass selective characteristics of the mass selective ion trap may be continuously varied. Therefore, reference in the claims to ions having mass to charge ratios within a first range being released at a first time t1 and ions having mass to charge ratios within a second range etc. being released at a second etc. time t2 should be construed as covering embodiments wherein the mass selective characteristics of the mass selective ion trap are varied in a stepped manner and embodiments wherein the mass selective characteristics of the mass selective ion trap are varied in a substantially continuous manner. Embodiments are also contemplated wherein the mass selective characteristics of the ion trap may be varied in a stepped manner for a portion of an operating cycle and in a continuous manner for another portion of the operating cycle.
At the first time t1 ions having mass to charge ratios outside of the first range are preferably substantially retained within the ion trap. Likewise, at the second time t2 ions having mass to charge ratios outside of the second range are preferably substantially retained within the ion trap.
The first range preferably has a minimum mass to charge ratio M1min and a maximum mass to charge ratio M1max. The value M1maxxe2x88x92M1min preferably falls within a range of 1-50, 50-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500 or  greater than 1500.
Similarly, the second range has a minimum mass to charge ratio M2min and a maximum mass to charge ratio M2max. The value M2maxxe2x88x92M2min preferably falls within a range of 1-50, 50-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500 or  greater than 1500.
Preferably, M1max greater than M2max and/or M1min greater than M2min i.e. the upper mass cut-off in the first range is preferably greater than the upper mass cut-off in the second range and/or the lower mass cut-off in the first range is preferably greater than the lower mass cut-off in the second range.
The control means preferably further controls the ion trap and the orthogonal acceleration Time of Flight mass analyser so that: (iv) at a third later time t3 after t1 and t2 but prior to tpush ions having mass to charge ratios within a third range are arranged to be substantially passed from the ion trap to the orthogonal acceleration Time of Flight mass analyser whilst ions having mass to charge ratios outside of the third range are not substantially passed to the orthogonal acceleration Time of Flight mass analyser; and wherein at the time tpush the electrode is arranged to orthogonally accelerate ions having mass to charge ratios within the first, second and third ranges.
At the third time t3 ions having mass to charge ratios outside of the third range are preferably substantially retained within the ion trap.
The third range preferably has a minimum mass to charge ratio M3min and a maximum mass to charge ratio M3max. The value M3maxxe2x88x92M3min preferably falls within a range of 1-50, 50-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500 or  greater than 1500.
Preferably, M2max greater than M3max and/or M2min greater than M3min.
The control means preferably further controls the ion trap and the orthogonal acceleration Time of Flight mass analyser so that: (v) at a fourth later time t4 after t1, t2 and t3 but prior to tpush ions having mass to charge ratios within a fourth range are arranged to be substantially passed from the ion trap to the orthogonal acceleration Time of Flight mass analyser whilst ions having mass to charge ratios outside of the fourth range are not substantially passed to the orthogonal acceleration Time of Flight mass analyser; and wherein at the time tpush the electrode is arranged to orthogonally accelerate ions having mass to charge ratios within the first, second, third and fourth ranges.
At the fourth time t4 ions having mass to charge ratios outside of the fourth range are preferably substantially retained within the ion trap.
The fourth range preferably has a minimum mass to charge ratio M4min and a maximum mass to charge ratio M4max. The value M4maxxe2x88x92M4min preferably falls within a range of 1-50, 50-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, 1300-1400, 1400-1500 or  greater than 1500.
Preferably, M3max greater than M4max and/or M3min greater than M4min. The electrode is not energised after time t1 and prior to tpush.
Ions may be released from the mass selective ion trap by mass-selective instability and/or by resonance ejection. If mass-selective instability is used to eject ions from the ion trap then the ion trap is either in a low pass mode or in a high pass mode. As such, M1max and/or M2max and/or M3max and/or M4max may in a high pass mode be at infinity. Likewise, in a low pass mode M1min and/or M2min and/or M3min and/or M4min may be zero. If resonance ejection is used to eject ions from the ion trap then the ion trap may be operated in either a low pass mode, high pass mode or bandpass mode. Other modes of operation are also possible.
According to another aspect of the present invention there is provided a mass spectrometer comprising: a 3D quadrupole ion trap; an orthogonal acceleration Time of Flight mass analyser arranged downstream of the 3D quadrupole ion trap, the orthogonal acceleration Time of Flight mass analyser comprising an electrode for orthogonally accelerating ions; and control means for controlling the ion trap and the electrode, wherein the control means causes: (i) at a first time t1 a first packet of ions having mass to charge ratios within a first range to be released from the ion trap; and (ii) at a second later time t2 after t1 a second packet of ions having mass to charge ratios within a second (different) range to be released from the ion trap; and then (iii) at a later time tpush after t1 and t2 the electrode to orthogonally accelerate the first and second packets of ions. The electrode is not energised after time t1 and prior to tpush.
Preferably, the control means further causes: (iv) at a time t3 after t1 and t2 but prior to tpush a third packet of ions having mass to charge ratios within a third (different) range to be released from the ion trap; and (v) at a time t4 after t1, t2 and t3 but prior to tpush a fourth packet of ions having mass to charge ratios within a fourth (different) range to be released from the ion trap.
Preferably, the first, second, third and fourth ranges are all different. Preferably, at least the upper mass cut-off and/or the lower mass cut-off of the first, second, third and fourth ranges are different. The width of the first, second, third and fourth ranges may or may not be the same.
Preferably, the first range has a maximum mass to charge ratio M1max, the second range has a maximum mass to charge ratio M2max, the third range has a maximum mass to charge ratio M3max, the fourth range has a maximum mass to charge ratio M4max, and wherein M1max greater than M2max greater than M3max greater than M4max. Alternatively, in the case of mass-selective instability M1max, M2max, M3max, M4max etc. may all be at infinity.
Preferably, the first range has a minimum mass to charge ratio M1min, the second range has a minimum mass to charge ratio M2min, the third range has a minimum mass to charge ratio M3min, the fourth range has a minimum mass to charge ratio M4max, and wherein M1min greater than M2min greater than M3min greater than M4min. Alternatively, in the case of mass-selective instability M1min, M2min, M3min, M4min etc. may all be at zero.
According to another aspect of the present invention, there is provided a method of mass spectrometry comprising: ejecting ions having mass to charge ratios within a first range from a mass selective ion trap whilst ions having mass to charge ratios outside of the first range are retained within the ion trap; then ejecting ions having mass to charge ratios within a second range from the mass selective ion trap whilst ions having mass to charge ratios outside of the second range are retained within the ion trap; and then orthogonally accelerating ions having mass to charge ratios within the first and second ranges, wherein the first and second ranges are different.
According to another aspect of the present invention, there is provided a method of mass spectrometry comprising releasing multiple packets of ions from a mass selective ion trap upstream of an electrode for orthogonally accelerating ions, wherein the multiple packets of ions are arranged to arrive at the electrode at substantially the same time. The ions are released according to their mass to charge ratios i.e. the ions are released in a mass to charge ratio selective manner.
According to another aspect of the present invention, there is provided a mass spectrometer comprising a mass selective ion trap upstream of an electrode for orthogonally accelerating ions, wherein in a mode of operation multiple packets of ions are released from the ion trap so that the multiple packets of ions arrive at the electrode at substantially the same time. The ions are released according to their mass to charge ratios i.e. the ions are released in a mass to charge ratio selective manner.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising substantially continuously releasing ions from a mass selective ion trap upstream of an electrode for orthogonally accelerating ions, wherein the ions are arranged to arrive at the electrode at substantially the same time. The ions are released according to their mass to charge ratios.
According to another aspect of the present invention there is provided a mass spectrometer comprising a mass selective ion trap upstream of an electrode for orthogonally accelerating ions, wherein in a mode of operation ions are substantially continuously released from the ion trap so that the ions arrive at the electrode at substantially the same time.
According to another aspect of the present invention, there is provided a mass spectrometer comprising: a mass selective ion trap; and an orthogonal acceleration Time of Flight mass analyser having an electrode for orthogonally accelerating ions into a drift region; wherein in a first mode of operation multiple packets of ions are progressively released from the mass selective ion trap and are sequentially or serially ejected into the drift region after different delay times and wherein in a second mode of operation multiple packets of ions are released so that the multiple packets of ions arrive at the electrode at substantially the same time.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising: progressively releasing multiple packets of ions from a mass selective ion trap so that the packets of ions are sequentially or serially ejected into a drift region of an orthogonal acceleration Time of Flight mass analyser by an electrode after different delay times; and then releasing multiple packets of ions from the mass selective ion trap so that the multiple packets of ions arrive at the electrode at substantially the same time.
As will be appreciated from above, two distinct main embodiments are contemplated. According to the first main embodiment ions having mass to charge values within a specific range are ejected from a mass selective ion trap such as a 3D quadrupole field ion trap upstream of the pusher electrode. Ions not falling within the specific range of mass to charge values preferably remain trapped within the ion trap.
The ion trap stores ions and can be controlled to eject either only those ions having a specific discrete mass to charge ratio, ions having mass to charge ratios within a specific range (bandpass transmission), ions having a mass to charge ratios greater than a specific value (highpass transmission), ions having a mass to charge ratios smaller than a specific value (lowpass transmission), or ions having mass to charge ratios greater than a specific value together with ions having mass to charge ratios smaller than another specific value (bandpass filtering).
The range of the mass to charge ratios of the ions released from the mass selective ion trap and the delay time thereafter when the pusher electrode orthogonally accelerates the ions in the region of the pusher electrode can be arranged so that preferably nearly all of the ions released from the ion trap are orthogonally accelerated. Therefore, it is possible to achieve a duty cycle of approximately 100% across a large mass range.
Ions which are not released from the ion trap when a first bunch of ions is released are preferably retained in the ion trap and are preferably released in subsequent pulses from the ion trap. For each cycle, ions with a different band or range of mass to charge values are released. Eventually, substantially all of the ions are preferably released from the ion trap. Since substantially all of the ions released from the ion trap are orthogonally accelerated into the drift region of the Time of Flight mass analyser, the duty cycle for ions of all mass to charge values may approach 100%. This represents a significant advance in the art.
According to a second main embodiment of the present invention ions are stored in a mass selective ion trap and are then released, preferably sequentially, in reverse order of mass to charge ratio. Ions with the highest mass to charge ratios are released first and ions with the lowest mass to charge ratios are released last.
Ions with high mass to charge ratios travel more slowly and so by releasing these ions first they have a head start over ions with lower mass to charge ratios. The ions may be accelerated to a constant energy by applying an appropriate voltage to the ion trap and may then be allowed to travel along a field free drift region. By appropriate design of the mass scan law of the 3D quadrupole field ion trap or other mass selective ion trap, ions may be ejected from the ion trap such that all ions irrespective of their mass to charge ratios arrive at the pusher electrode at substantially the same time and with the same energy. This enables the duty cycle for ions of all mass to charge values to be raised to approximately 100% and again represents a significant advance in the art.
Where reference is made in the present application to a mass selective ion trap it should be understood that the ion trap is selective about the mass to charge ratios of the ions released from the ion trap unlike a non-mass selective ion trap wherein when ions are released from the ion trap they are released irrespective of and independent of their mass to charge ratio.